Evidence of apoptosis in chronic alcoholic skeletal myopathy
Evidence of apoptosis in chronic alcoholic skeletal myopathy
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DOI：
10.1016/j.humpath.2003.07.017
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发表时间：
2003-12-01
期刊：
影响因子：
3.3
通讯作者：
Urbano-Márquez, A
中科院分区：
文献类型：
--
作者：
Fernández-Solà, J;Nicolás, JM;Urbano-Márquez, A
细胞凋亡是细胞程序性死亡的一种常见机制，参与了酒精性器官损伤的发病机制。实验研究表明，酒精介导了心肌细胞的凋亡。酒精中毒时骨骼肌和心肌损伤之间的关系促使我们考虑细胞凋亡在骨骼肌病发病机制中的可能作用。我们前瞻性地评估了连续选择的30名高剂量、营养良好的慢性酒精饮用者和12名非酒精对照组的骨骼肌活检中的细胞凋亡。进行饮酒、肌力测定、三角肌活检免疫组织化学和形态计量学分析。采用原位末端标记法、bax和bcl2免疫组织化学方法检测细胞凋亡。与对照组相比，慢性酒精中毒患者TUNEL(2.35%+/-0.25%vs0.18%+/-0.03%，P<；0.001)、bax(9.16%+/-2.00%vs0.66%+/-0.22%，P<；0.001)和bc1-2蛋白(8.08%+/-0.20%vs0.83%+/-0.20%，P=0.001)的细胞凋亡指数显著升高。此外，有骨骼肌病的酗酒者细胞凋亡指数高于无骨骼肌病者(TUNEL分别为3.04%+/-0.36%和1.65%+/-0.26%，P=0.004；BAX分别为17.00%+/-2.78%和1.33%+/-0.22%，P<；0.001；bcl-2分别为15.13%+/-3.2%和1.03%+/-0.33%，P<；0.001)。我们的结论是，高剂量酒精消费者的骨骼肌中存在细胞凋亡，主要是那些受肌病影响的人。然而，酒精性慢性骨骼肌病细胞凋亡的具体发病机制尚不清楚。(C)2003 Elsevier Inc.保留所有权利。
Apoptosis is a common mechanism of programmed cell death that has been implicated in the pathogenesis of alcohol-induced organ damage. Experimental studies have suggested alcohol-mediated apoptosis in cardiac muscle. The relationship between skeletal and cardiac muscle damage in alcoholism led us to consider the possible role of apoptosis in the pathogenesis of skeletal myopathy. We prospectively evaluated apoptosis in skeletal muscle biopsies of 30 consecutively selected male high-dose well-nourished chronic alcohol consumers and 12 nonalcoholic controls. Alcohol consumption, evaluation of muscle strength by myometry, and deltoid muscle biopsy with immunohistochemical and morphometric analysis were performed. Apoptosis was assessed by TUNEL, BAX, and BCL-2 immunohistochemical assays. Chronic alcoholics compared with controls showed a significantly higher apoptotic index in TUNEL (2.35% +/- 0.25% versus 0.18% +/- 0.03%, P < 0.001), BAX (9.16% +/- 2.00% versus 0.66% +/- 0.22%, P < 0.001), and BCL-2 muscle assays (8.08% +/- 0.20% versus 0.83% +/- 0.20%, P = 0.001), respectively. In addition, these apoptotic indexes were higher in alcoholics with skeletal myopathy compared with in those without skeletal myopathy (3.04% +/- 0.36% versus 1.65% +/- 0.26%, P = 0.004 for TUNEL; 17.00% +/- 2.78% versus 1.33% +/- 0.22%, P < 0.001 for BAX; and 15.13% +/- 3.2% versus 1.03% +/- 0.33%, P < 0.001 for BCL-2 assays, respectively). We conclude that apoptosis is present in the skeletal muscle of high-dose alcohol consumers, mainly in those affected by myopathy. However, the specific pathogenic mechanism of apoptosis in chronic skeletal myopathy in alcoholics remains to be elucidated. (C) 2003 Elsevier Inc. All rights reserved.